School of Biological Sciences, University of Queensland, Brisbane, Australia.
Victor Chang Cardiac Research Institute, Sydney, Australia.
Science. 2020 Nov 6;370(6517). doi: 10.1126/science.aax8137.
Interactions of transcription factors (TFs) with DNA regulatory sequences, known as enhancers, specify cell identity during animal development. Unlike TFs, the origin and evolution of enhancers has been difficult to trace. We drove zebrafish and mouse developmental transcription using enhancers from an evolutionarily distant marine sponge. Some of these sponge enhancers are located in highly conserved microsyntenic regions, including an enhancer in the - region. We found that enhancers in humans and mice share a suite of TF binding motifs with sponges, and that they drive gene expression patterns similar to those of sponge and endogenous enhancers in zebrafish. Our results suggest the existence of an ancient and conserved, yet flexible, genomic regulatory syntax that has been repeatedly co-opted into cell type-specific gene regulatory networks across the animal kingdom.
转录因子 (TFs) 与 DNA 调控序列（称为增强子）的相互作用，决定了动物发育过程中的细胞身份。与 TFs 不同，增强子的起源和进化一直难以追踪。我们使用来自进化上遥远的海洋海绵的增强子来驱动斑马鱼和小鼠的发育转录。这些海绵增强子中的一些位于高度保守的微同线性区域，包括 - 区域中的一个增强子。我们发现人和小鼠中的 增强子与海绵具有一套共同的 TF 结合基序，并且它们在斑马鱼中驱动与海绵和内源性 增强子相似的基因表达模式。我们的结果表明，存在一种古老而保守的、但具有灵活性的基因组调控语法，它在动物王国中被反复重新用于细胞类型特异性基因调控网络。
